The purpose of the proposed studies is to define as precisely as possible the processes involved in iron uptake, utilization or storage, and eventually release by cells in key tissues throughout the body and to examine the biochemical and functional changes resulting from iron deficiency. The investigations will be focused in three major areas: 1) iron binding to specific receptors on the placenta and examination of transplacental iron transfer; 2) further examination of functional heterogeneity of iron atoms bound to transferrin of man, rats, and other experimental animals; and 3) a study of the effects of iron deficiency (and its correction) on skeletal muscle function. Utilization of a microvillus vesicle preparation of human placenta is expected to aid in the isolation and purification of receptor sites for transferrin-bound iron. Functional heterogeneity of transferrin in the rat and other species may be due to the presence of isotransferrins or differences in the iron-binding sites. These possibilities may be resolved by studying the function of transferrin fragments with single iron binding sites or by separation of isotransferrin species. Muscle function in an isolated hind limb preparation of the rat will be studied in iron deficient rats before and after iron treatment to determine changes in iron containing compounds and enzyme systems.